Analysis Of Systems Influencing Renal Hemodynamics And Sodium Excretion. I. Biochemical Systems Theory

SHARON L. REILLY, CHARLES F. SING, AND MICHAEL A. SAVAGEAU

University of Michigan Medical School, Ann Arbor

and

STEPHEN T. TURNER

Dept. of lnternal Medicine, Mayo Clinic

Abstract--In this article we present a new methodology--Biochemical Systems Theory

and Analysis---as an alternative to traditional parametric statistical procedures for investigating

differences between risk groups in a population. We review the systems theory and

how it can be used to represent a model of processes influencing renal hemodynamics and

sodium (Na § excretion. We also discuss the potential for new measures of the biology of

common diseases that can emerge from a synergism between systems theory and population-

based statistical approaches.

Key Words: Systems theory, Hypertension, Renal Hemodynamics, Genetics, Common

Diseases

Introduction

Common diseases, such as hypertension, coronary artery disease, and cancer, are the

clearest examples of biological complexity. One property of complex systems that all

common diseases share is a complex etiological hierarchy (Sing and Reilly, 1993). This

hierarchy consists of many genes (level I) determining the biochemical, physiological and

anatomical systems (level II) that are associated with the initiation, progression, and manifestation

of the disease (level III). Environmental factors, such as diet and lifestyle, also

play a key role in determining risk of disease since they influence each of these etiological

levels. As information at these etiological levels continues to accumulate there is an increasing

need to determine if this piecewise knowledge can be integrated to simultaneously

model the relationship within and between the three levels for a common disease.

Systems analysis is one class of quantitative methods that has been successful in modeling

many different types of physiological and biochemical processes (level II) and their

impact on traits associated with a particular disease (level III) (Guyton et al., 1974; Yates,

1980; Berman, 1984). In the field of hypertension research, Guyton et al. (1967) were

among of the first to emphasize the utility of systems analysis in organizing biological

concepts into information about physiological systems involved in the regulation of arterial

blood pressure. Using control theory and animal models, Guyton and colleagues developed

systems models of the circulatory system to investigate the physiological basis of hypertension

and other circulatory anomalies. These models ranged from the simple to the

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